MYCOLab Ai Logo - gold and army green

Improving the production of micafungin precursor FR901379 in Coleophoma empetri using heavy-ion irradiation and its mechanism analysis

Summary

Scientists successfully improved the production of a key ingredient for the antifungal drug micafungin by using heavy-ion radiation to create improved strains of a fungus called Coleophoma empetri. The best mutant strain produced over 250% more of the desired compound than the original strain. By analyzing the genetic changes in these improved strains, researchers identified specific genes related to fungal structure and metabolism that contribute to higher production, providing insights for future improvements to the manufacturing process.

Background

Micafungin is a semisynthetic echinocandin antifungal agent derived from the fungal natural product FR901379 produced by Coleophoma empetri. The organism has limited biosynthetic capacity for the desired metabolite, making production challenging. Heavy-ion irradiation has shown promise as a novel breeding method for creating high-yield mutants in filamentous fungi.

Objective

This study aimed to improve FR901379 production in C. empetri using heavy-ion beam irradiation and to elucidate the mechanisms of DNA damage repair and high-yield production through genomic and transcriptomic analysis.

Results

Two rounds of heavy-ion irradiation produced mutants with 1.1 g/L FR901379 yield, representing a 253.7% increase over the wild-type strain. NHEJ-deficient mutants showed higher mutation frequencies including increased InDels, SNPs, and structural variations. Mutations in genes encoding oxidoreductases, membrane proteins, kinases, and transcription factors correlated with enhanced production and altered morphology.

Conclusion

Heavy-ion irradiation effectively generates high-yield FR901379 mutants with improved fermentation performance and morphological characteristics. Comparative genomic analysis reveals mutations in genes critical for morphological differentiation. The upregulation of core biosynthetic gene mcfA contributes to increased FR901379 production, providing a promising chassis for further metabolic engineering.
  • Published in:Mycology,
  • Study Type:Experimental Mutagenesis and Genomic Analysis,
  • Source: 10.1080/21501203.2024.2426484, PMID: 40415921
Scroll to Top